Sequential micro-PET based brain imaging in the unilateral labyrithectomy rat model: Insights to compensatory brain plasticity

Objectives: Characterization of dynamic brain activation patterns in vestibular damage and compensation.

Methods: Unilateral labyrinthectomy (UL) was performed by drilling into the vestibule and removing its contents in 3-month old Sprague-Dawley rats (n=4). As a control group, animals were given a surgical sham treatment identical to the UL procedure, but without damage to the inner ear (n=4). Sequential [18F]-Fluoro-desoxyglucose micro-PET imaging was done in all animals on day 1 before and days 1, 2, 5 and 12 after UL and sham surgery. At same time points vestibular deficits were scored for the components nystagmus, head tilt and postural asymmetry. Individual brain images were normalized to a rat brain template and mean brain activation maps calculated by group analysis.

Results: Dynamic changes of the regional cerebral metabolic rate for glucose (rCMRglc) could be shown in the UL but not in the sham group, which could be categorized into four stages: 1) Stage of vestibular imbalance: At day 1 after UL a significant asymmetry of rCMRglc appears showing reduced glucose consumption in the ipsilateral vestibular nucleus, contralateral tegmental mesencephalic nuclei (including the interstitial nucleus of Cajal, parabrachial nucleus, raphe nucleus), the contralateral posterolateral thalamus and temporoparietal cortex and increased glucose consumption in the ipsilateral posterolateral thalamus. 2) Stage of early vestibular compensation: At day 2 after UL rCMRglc equalizes in the vestibular nuclei and the mesencephalic nuclei at a level below baseline parallel with concomitant gradual normalization of behavioural signs of vestibular imbalance. 3) Stage of vestibular hypercompensation: At day 5 after UL the contralateral vestibular nucleus, ipsilateral tegmental mesencephalic nuclei and posterolateral thalamus show significant increase in rCMRglc. 4) Stage of late vestibular compensation: At day 12 after UL rCMRglc of the vestibular nuclei, the tegmental mesencephalic nuclei, the posterolateral thalamus and the cortex was symmetric and back to baseline.

Conclusions: In the present study, highly dynamic changes of brain activation are shown in the time course after unilateral vestibular damage reflecting compensatory mechanisms. Four stages can be differentiated based on rCMRglc patterns, which correspond to normalization of behavioural signs of vestibular damage. In summary, vestibular compensation is a paradigm for adult brain plasticity in sensory systems.